HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE

人前列腺 3A 羟基类固醇脱氢酶

基本信息

项目摘要

DESCRIPTION (Adapted from the Applicant's Abstract): In androgen target tissues 3a-hydroxysteroid dehydrogenases (3a-HSDs) may regulate the occupancy of androgen receptor (AR) by interconverting 5a-dihydrotestosterone (5a-DHT, a potent androgen) with 5a-androstane-3a,17b-diol (3a-diol, a weak androgen). We have obtained type 2 and type 3 3a-HSD cDNAs expressed in human prostate and overexpressed the enzymes in E. coli. Kinetic studies of these recombinant enzymes show that type 3 3a-HSD functions as both a 3a-and 17b-HSD to inactivate active androgens, whereas, type 3 3a-HSD interconverts 5a-DHT with 3a- diol. Levels of 3a-HSD mRNA were higher in primary cultures of prostatic epithelial cells than stromal cells; and elevated levels of 3a-HSD mRNA were observed in primary cultures of epithelial cells derived from benign prostatic hyperplasia and prostatic carcinoma tissues. Expression of steady state levels of 3a-HSD mRNA is up-regulated by epidermal growth (EGF) in human prostatic cell lines, LNCaP (androgen sensitive) and PC3 (androgen insensitive). The focus of this proposal is to examine the physiological functions of type 2 and type 3 3a-HSD in regulating androgen metabolism and their activities in modulating prostatic cell proliferation will be investigated. This will be accomplished by stably transfecting type 2 and type 3 3a-HSD cDNAs into these cells. Second, levels of endogenous type 2 and type 3 3a-HSD transcripts will be examined in RNA extracted from the cell lines and normal prostate using ribonuclease protection assay (RPA). Third, EGF-regulated type 2 and type 3 3a-HSD mRNA levels will be examined using RPA. Changes in 3a-HSD expression mediated by EGF will be examined in cell lysates by immunotitration of the enzyme activity. Fourth, to understand the constitutive and EGF- regulated type 2 and type 3 3a-HSD expression in prostatic cells, the 5'-flanking regions of the 3a-HSD genes will be sequenced and cis-acting elements responsible for transcription regulation of two isoforms will be identified.
描述(改编自申请人的摘要):在雄激素靶向中 组织3 α-羟基类固醇脱氢酶(3a-HSDs)可以调节 雄激素受体(AR)通过相互转换占据 5 α-双氢睾酮(5 α-DHT,一种强效雄激素), 5a-雄甾烷-3a,17 b-二醇(3a-二醇,弱雄激素)。 我们得到了 2型和3型3a-HSD cDNA在人前列腺中表达,并过表达 E.杆菌 这些重组酶的动力学研究表明, 3型3a-HSD作为3a-HSD和17 b-HSD发挥作用, 雄激素,而3型3 α-HSD将5 α-DHT与3 α-二醇相互转化。 前列腺原代培养物中3a-HSD mRNA水平较高 上皮细胞比基质细胞; 3a-HSD mRNA水平升高, 在来源于良性肿瘤的上皮细胞的原代培养物中观察到, 前列腺增生和前列腺癌组织。 稳态表达式 3a-HSD mRNA的状态水平被表皮生长(EGF)上调, 人前列腺细胞系,LNCaP(雄激素敏感)和PC 3(雄激素 不敏感)。 这个建议的重点是研究类型的生理功能 2型和3型3a-HSD调节雄激素代谢及其活性 调节前列腺细胞增殖。 这将 通过将2型和3型3a-HSD cDNA稳定地转染入 这些细胞。 第二,内源性2型和3型3a-HSD水平 将在从细胞系和正常细胞系中提取的RNA中检查转录物。 前列腺使用核糖核酸酶保护测定(RPA)。 第三,EGF调节 使用RPA检测2型和3型3a-HSD mRNA水平。 变化 将在细胞裂解物中通过以下方法检测EGF介导的3a-HSD表达: 酶活性的免疫滴定。 第四,了解 组成型和EGF调节的2型和3型3a-HSD表达, 在前列腺细胞中,3a-HSD基因的5 '-侧翼区将被 负责转录调控的序列顺式作用元件 两种异构体将被识别。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
5alpha-Androstane-3alpha,17beta-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation.
5alpha-Androstane-3alpha,17beta-diol 激活类似于表皮生长因子响应途径的途径,刺激人前列腺癌 LNCaP 细胞增殖。
  • DOI:
    10.1038/sj.pcan.4500761
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Zimmerman,RA;Dozmorov,I;Nunlist,EH;Tang,Y;Li,X;Cowan,R;Centola,M;Frank,MB;Culkin,DJ;Lin,H-K
  • 通讯作者:
    Lin,H-K
Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival.
雄激素受体信号传导是雄激素敏感的人类前列腺癌细胞增殖和存活所必需的。
  • DOI:
    10.1186/1475-2867-5-8
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Yang,Qing;Fung,Kar-Ming;Day,WandaV;Kropp,BradleyP;Lin,Hsueh-Kung
  • 通讯作者:
    Lin,Hsueh-Kung
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HSUEH-KUNG LIN其他文献

HSUEH-KUNG LIN的其他文献

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{{ truncateString('HSUEH-KUNG LIN', 18)}}的其他基金

HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE
人前列腺 3A 羟基类固醇脱氢酶
  • 批准号:
    2614194
  • 财政年份:
    1998
  • 资助金额:
    $ 14.55万
  • 项目类别:
HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE
人前列腺 3A 羟基类固醇脱氢酶
  • 批准号:
    6177945
  • 财政年份:
    1998
  • 资助金额:
    $ 14.55万
  • 项目类别:
HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE
人前列腺 3A 羟基类固醇脱氢酶
  • 批准号:
    2906335
  • 财政年份:
    1998
  • 资助金额:
    $ 14.55万
  • 项目类别:
HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE
人前列腺 3A 羟基类固醇脱氢酶
  • 批准号:
    6381385
  • 财政年份:
    1998
  • 资助金额:
    $ 14.55万
  • 项目类别:
HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE
人前列腺 3A 羟基类固醇脱氢酶
  • 批准号:
    6405358
  • 财政年份:
    1998
  • 资助金额:
    $ 14.55万
  • 项目类别:
HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE
人前列腺 3A 羟基类固醇脱氢酶
  • 批准号:
    6071811
  • 财政年份:
    1998
  • 资助金额:
    $ 14.55万
  • 项目类别:

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    10431620
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Defining the impact of androgens on uterine immune cell function during endometrial tissue repair
确定子宫内膜组织修复过程中雄激素对子宫免疫细胞功能的影响
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